None listed
Conditions
Brief summary
The primary purpose of this trial is to assess whether the addition of durvalumab to patients who have achieved less than partial response to 4 cycles of lenalidomide and dexamethasone will cause an improvement in disease progression free survival. Who is it for? You may be eligible to participate in this trial if you are aged 18 years or over, have been newly diagnosed with multiple myeloma and are not a candidate for high dose chemotherapy and autologous stem cell transplant. Study details Eligible participants will all receive lenalidomide and dexamethasone treatment in 28 day cycles, with those patients failing to adequately respond receiving durvalumab in addition. Treatment will continue until disease progression, unacceptable toxicity or patients otherwise coming off study. Participants will be required to have blood samples taken at the beginning of each cycle along with a medical examination to monitor treatment safety and whether it is effectively treating the myeloma. It is hoped that the findings of this trial will establish the benefits of durvalumab in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma patients early in the course of their disease.
Interventions
All patients given Lenalidomide as oral capsules, 25mg, daily on days 1 to 21 followed by a 7-day rest in a 28-day cycle and Dexamethasone as oral 4mg tablets, at a dose of 40mg (20mg for patients age >75 years) on days 1,8,15 and 22. Those patients not achieving partial response after 4 weeks of treatment, or very good partial response after 6 weeks of treatment or complete response after 9 weeks of treatment will be given Durvalumab at a dose of 1500mg IV on day 1 of the 28-day cycle. The IV i
All patients given Lenalidomide as oral capsules, 25mg, daily on days 1 to 21 followed by a 7-day rest in a 28-day cycle and Dexamethasone as oral 4mg tablets, at a dose of 40mg (20mg for patients age >75 years) on days 1,8,15 and 22. Those patients not achieving partial response after 4 weeks of treatment, or very good partial response after 6 weeks of treatment or complete response after 9 weeks of treatment will be given Durvalumab at a dose of 1500mg IV on day 1 of the 28-day cycle. The IV infusion for subjects will be approximately 1 hour in duration. Treatment will be given until disease progression or unacceptable toxicity, whichever occurs first. All dosing is recorded by hospital staff. Drug accountability logs will be used by the hospital staff.
Sponsors
Australia Myeloma Research Consortium
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or Female patients, greater than or equal to 18 years of age 2. Either: a). Treatment-naive multiple myeloma (diagnosis of MM as per Internatioal Myeloma Working Group definition) (ie. no prior therapies (except radiotherapy or short couse of corticosteroids equivalent to dexamethasone 160mg in the last 28 days)) OR b). MM undergoing first line treatment with lenalidomide and dexamethasone AND have not completed four cycles of treatment AND is responding to treatment (ie. have not had progressive disease). 3. Measureable disease at diagnosis: a). Serum M-protein greater than or equal to 5 g/L, or b).Urine M-protein greater than or equal to 200 mg/24 hour, or c). In patients without detectable serum or urine M-protein, serum free light chain (SFLC) greater than 100 mg/L (involved light chain) and an abnormal serum k/l ratio or For IgA patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA) greater than or equal to 7500 mg/L (7.5 g/L). 4. Must be deemed ineligible for upfront autolgous stem cell transplant (ASCT). 5. ECOG performance status 0-2 6. Adequate liver function ( ALT, AST and GGT less than or equal to 2.5 x institutional upper limit of normal; GGT less than or equal to 1.5 x institutional upper limit of normal ) 7. Creatinine clearance greater than 15ml/min 8. Platelet count greater than or equal to 50 x 109 (greater than or equal to 30 if bone marrow involvment by CD138+ myeloma cells exceeds 50percent of all nucleated cells on IHC). 9. Absolute neutrophil count greater than or equal to 1.0 x 109 (can be supported by growth factor support) 10. No contraindication to the use of any of the study drugs 11. No concomitant steroids other than dexamethasone outlined in this protocol 12. Patient has voluntarily agreed and has given written informed consent. 13. Life expectancy of greater than 12 weeks 14. All patients must be registered on and abide by the Celgene i-access Risk Management Program before receiving first dose of lenalidomide (www.iaccesscelgene.com). This program states the following requirement: a). All females of childbearing potential (FCBP) must agree to have a negative pregnancy tests within 7 days of commencing each new cycle of lenalidomide and use two reliable methods of contraception simultaneously or to practice complete abstinence from any sexual contact during the following time periods related to this study: 1) for at least 28 days before starting study; 2) while participating in the study; 3) dose interruptions; and 4) for at least 28 days after study treatment discontinuation. The two methods of reliable contraception must include one highly effective method and one additional effective method). b). All male participants must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following study drug discontinuation, even if he has undergone a successful vasectomy
Exclusion criteria
1. Patients with monoclonal gammopathy of uncertain significance or smouldering myeloma (as defined by IMWG) 2. Primary amyloidosis 3. Subjects who have had clinical evidence of central nervous system (CNS) or CNS multiple myeloma, or plasma cell leukemia 4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements 5. Pregnant or lactating women. 6. Known Hepatitis B or Hepatitis C requiring treatment, HIV infection, other immunosuppressive therapy or autoimmune disease 7. Prior history of malignancies, other than MM, unless the subject has been free of the disease for greater than or equal to 5 years with the exception of the following non-invasive malignancies: a. Basal cell carcinoma of the skin or level 1 melanoma that has been resected. b. Squamous cell carcinoma of the skin c. Carcinoma in situ of the cervix d. Carcinoma in situ of the breast e. Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative 8. Known or suspected hypersensitivity to the excipients contained in the formulation of durvalumab, lenalidomide, or dexamethasone. 9. Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of initiating study treatment 10. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis, Crohn’s disease], diverticulitis with the exception of a prior episode that has resolved or diverticulosis, celiac disease, irritable bowel disease, or other serious gastrointestinal chronic conditions associated with diarrhea; systemic lupus erythematosus; Wegener’s syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves’ disease; rheumatoid arthritis; hypophysitis, uveitis) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion: a. Subjects with vitiligo or alopecia; b. Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement; or c. Subjects with psoriasis not requiring systemic treatment; 11. Subject has incidence of gastrointestinal disease that may significantly alter the absorption of lenalidomide. 12. Receipt of live, attenuated vaccine within 30 days prior to the first dose of durvalumab (NOTE: subjects, if enrolled, should not receive live vaccine during the study and for 30 days after the last dose of durvalumab) 13. Unable or unwilling to undergo protocol required thromboembolism prophylaxis. 14. Females who are pregnant, nursing or breastfeeding, or intend to become pregnant during the participation to the study 15. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study. 16. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study 17. Any condition that confounds the ability to interpret data from the study
Outcome results
None listed